Benzodiazepines amine functionalization reactions

New amine functionalization reactions have been applied to the functionalization of benzodiazepines, for example, twofold methylation of 2,3,4,5-tetrahydro-lff-benzo[e][l,4]diazepine was achieved using carbon dioxide and phenylsilane with ruthenium catalysis (13AGE9568). A range of readily available 3,4-dihydro-lH-benzo[e][l,4]diazepine-2,5-diones underwent iV-acylation followed by a dehydrative ring-contraction rearrangement process to afford the corresponding oxazoloquinolinones (13OL1052). 

All substrates mentioned in the previous chapter easily undergo palladium-catalyzed aminocarbonylation also. It should be mentioned that even allylic carbonates instead of halides could be converted into carboxamides by this method, as it vas demonstrated during the total synthesis of antillatoxin [94]. The use of aryl chlorides is somewhat restricted owing to the low reactivity ofthese type of substrates in oxidative addition to palladium(O), as well as the competitive amination observed, for example, in the reaction of 1-chloroisoquinoline [95]. Functionalization of a great number of pharmaceutically important skeletons, for example, steroids [96-99], tropenes [100], benzodiazepines [101], indoles [102], benzo[c[quinolizine derivatives [103], and quinolones [104], have been carried out. 

Kaur et al. (2012) carried out microwave-assisted synthesis of 2-hetryl amino substituted novel analogs of l,4-benzodiazepine-5-piperidinyl carboxamides. The 2-iminothioethyl ether derivatives undergo smooth nucleophilic displacement reaction with variety of hetryl amines and afforded products in excellent yields (90%) in 2-6 min. under microwave irradiation. They have highlighted the importance of the incorporation of some pharmacophores such as 2-aminopyridinyl, pyrimidinyl, and benzothiazolyl in 1,4-benzodiazepine nucleus. The amide functionality (the CO-NH group) in the seven membered heterocyclic ring of 1,4-benzodiazepine nucleus is the only active functional group present in this molecule, which will provide an important site for the incorporation of a wide variety of heterocycles (and fused heterocycles) and heterocycle appended structures in this molecule. 

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